Table 2.
Patients with at least one AE by CKD category at baseline
| Placebo | EMPA 10/25 mg | |||
|---|---|---|---|---|
| Category | n/N (%) | Rate, 100 patient-years (95% CI) | n/N (%) | Rate, 100 patient-years (95% CI) |
| SAEs | ||||
| Overall | 1,204/4,904 (24.6) | 18.61 (17.57–19.69) | 2,161/10,177 (21.2) | 15.52 (14.88–16.19) |
| G3A | 209/519 (40.3) | 27.18 (23.62–31.12) | 354/1,003 (35.3) | 22.46 (20.19–24.93) |
| G3B | 113/277 (40.8) | 31.16 (25.69–37.46) | 177/445 (39.8) | 26.81 (23.00–31.06) |
| G4 | 13/52 (25.0) | 29.93 (15.94–51.17) | 28/71 (39.4) | 41.31 (27.46–59.69) |
| AEs leading to treatment discontinuation | ||||
| Overall | 565/4,904 (11.5) | 7.40 (6.80–8.04) | 1,033/10,177 (10.2) | 6.43 (6.05–6.84) |
| G3A | 100/519 (19.3) | 10.37 (8.44–12.61) | 179/1,003 (17.8) | 9.26 (7.95–10.72) |
| G3B | 62/277 (22.4) | 13.10 (10.05–16.79) | 113/445 (25.4) | 14.17 (11.68–17.03) |
| G4 | 10/52 (19.2) | 21.47 (10.30–39.47) | 14/71 (19.7) | 15.70 (8.59–26.35) |
| Hypoglycemia | ||||
| Overall | 1,045/4,904 (21.3) | 16.32 (15.35–17.34) | 2,067/10,177 (20.3) | 15.69 (15.02–16.38) |
| G3A | 177/519 (34.1) | 24.02 (20.62–27.83) | 268/1,003 (26.7) | 17.20 (15.21–19.39) |
| G3B | 91/277 (32.9) | 24.23 (19.51–29.75) | 141/445 (31.7) | 22.85 (19.24–26.95) |
| G4 | 23/52 (44.2) | 67.50 (42.80–101.23) | 24/71 (33.8) | 39.34 (25.21–58.52) |
| Urinary tract infection | ||||
| Overall | 691/4,904 (14.1) | 9.70 (8.99–10.46) | 1,382/10,177 (13.6) | 9.27 (8.79–9.77) |
| G3A | 84/519 (16.2) | 9.18 (7.32–11.37) | 200/1,003 (19.9) | 11.36 (9.84–13.05) |
| G3B | 62/277 (22.4) | 13.69 (10.49–17.54) | 101/445 (22.7) | 13.98 (11.39–16.99) |
| G4 | 5/52 (9.6) | 10.24 (3.32–23.89) | 18/71 (25.4) | 25.19 (14.93–39.81) |
| Genital infection | ||||
| Overall | 75/4,904 (1.5) | 0.85 (0.75–1.20) | 565/10,177 (5.6) | 3.54 (3.25–3.84) |
| G3A | 8/519 (1.5) | 0.79 (0.34–1.56) | 54/1,003 (5.4) | 2.75 (2.06–3.58) |
| G3B | 2/277 (0.7) | 0.39 (0.05–1.43) | 15/445 (3.4) | 1.78 (1.00–2.94) |
| G4 | 0/52 (0) | 0 | 1/71 (1.4) | 1.13 (0.03–6.28) |
| Volume depletion | ||||
| Overall | 147/4,904 (3.0) | 1.89 (1.60–2.23) | 320/10,177 (3.1) | 1.97 (1.76–2.20) |
| G3A | 33/519 (6.4) | 3.38 (2.32–4.74) | 63/1,003 (6.2) | 3.22 (2.48–4.12) |
| G3B | 19/277 (6.9) | 3.95 (2.38–6.17) | 28/445 (6.3) | 3.43 (2.28–4.95) |
| G4 | 6/52 (11.5) | 12.04 (4.42–26.19) | 7/71 (9.8) | 8.22 (3.30–16.93) |
| Edema | ||||
| Overall | 278/4,904 (5.7) | 3.67 (3.25–4.12) | 269/10,177 (2.6) | 1.65 (1.46–1.86) |
| G3A | 51/519 (9.8) | 5.37 (4.00–7.06) | 49/1003 (4.9) | 2.48 (1.84–3.28) |
| G3B | 38/277 (13.7) | 8.12 (5.75–11.15) | 36/445 (8.1) | 4.42 (3.10–6.12) |
| G4 | 5/52 (9.6) | 11.77 (3.82–27.47) | 1/71 (1.4) | 1.11 (0.03–6.18) |
| Bone fracture | ||||
| Overall | 134/4,904 (2.7) | 1.72 (1.44–2.04) | 233/10,177 (2.3) | 1.42 (1.25–1.62) |
| G3A | 26/519 (5.0) | 2.60 (1.79–3.81) | 37/1,003 (3.7) | 1.86 (1.31–2.56) |
| G3B | 12/277 (4.3) | 2.40 (1.24–4.19) | 20/445 (4.5) | 2.40 (1.46–3.70) |
| G4 | 1/52 (1.9) | 2.06 (0.05–11.49) | 0/71 (0) | 0 |
| Falls | ||||
| Overall | 87/4,904 (1.8) | 1.11 (0.89–1.37) | 197/10,177 (1.9) | 1.20 (1.04–1.38) |
| G3A | 17/519 (3.3) | 1.70 (0.99–2.72) | 30/1,003 (3.0) | 1.50 (1.01–2.15) |
| G3B | 10/277 (3.6) | 2.01 (0.97–3.70) | 11/445 (2.5) | 1.30 (0.65–2.33) |
| G4 | 1/52 (1.9) | 2.06 (0.05–11.49) | 1/71 (1.4) | 1.11 (0.03–6.18) |
| Hyperkalemia | ||||
| Overall | 90/4,904 (1.8) | 1.15 (0.92–1.41) | 119/10,177 (1.2) | 0.72 (0.60–0.86) |
| G3A | 23/519 (4.4) | 2.31 (1.47–3.47) | 37/1,003 (3.7) | 1.86 (1.31–2.56) |
| G3B | 18/277 (7.6) | 3.73 (2.21–5.89) | 15/445 (3.4) | 1.78 (1.00–2.93) |
| G4 | 3/52 (6) | 6.16 (1.27–17.99) | 1/71 (1.4) | 1.11 (0.03–6.21) |
| ARF | ||||
| Overall | 169/4,904 (3.4) | 2.18 (1.86–2.53) | 291/10,177 (1.2) | 1.78 (1.58–2.00) |
| G3A | 48/519 (9.2) | 4.92 (3.63–6.53) | 86/1,003 (8.6) | 4.44 (3.55–5.48) |
| G3B | 37/277 (13.3) | 7.85 (5.53–10.83) | 57/445 (12.8) | 7.22 (5.47–9.35) |
| G4 | 6/52 (11.5) | 13.87 (5.09–30.19) | 9/71 (12.7) | 10.85 (4.96–20.59) |
| Lower limb amputation* | ||||
| Overall | 46/4,904 (0.9) | 0.52 (0.38–0.69) | 95/10,177 (0.1) | 0.52 (0.42–0.63) |
| G3A | 11/519 (2.1) | 0.92 (0.46–1.65) | 17/1,003 (1.7) | 0.74 (0.43–1.18) |
| G3B | 7/277 (2.5) | 1.22 (0.49–2.51) | 10/445 (2.2) | 0.95 (0.46–1.75) |
| G4 | 0/52 (0) | 0 | 4/71 (5.6) | 3.59 (0.98–9.20) |
Exposure-adjusted incidence rates were calculated per 100 patient-years as 100 × n / T, where n was the number of participants with the event and T the total patient-years at risk for the event. Patient-years at risk were defined as the time from the first dose of study treatment to the onset of the first event (for patients with an event) or to the last dose plus 7 days (for those without an event). The eGFR was calculated using the CKD-EPI equation. CKD categories by eGFR: G3A, 45 to <60 mL/min/1.73 m2; G3B, 30 to <45 mL/min/1.73 m2; G4, 15 to <30 mL/min/1.73 m2. Frequencies n/N = patients with one or more events of all patients who received one or more doses of study drug. EMPA 10/25, empagliflozin 10 or 25 mg.
Data from the EMPA-REG OUTCOME trial only. No amputations were reported for the four patients with missing baseline eGFR values.